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Indications of that migration of stem cells is influenced by the extra cellular matrix architecture in the mammalian intervertebral disc region

Journal article
Authors Helena Barreto Henriksson
Papadimitriou Nicolaos
Sarah Tschernitz
Emilia Svala
Eva Skiöldebrand
Sara H Windahl
Katarina Junevik
Helena Brisby
Published in Tissue & Cell
Volume 47
Issue 5
Pages 439–455
ISSN 0040-8166
Publication year 2015
Published at Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
Centre for Bone and Arthritis Research
Institute of Clinical Sciences, Department of Orthopaedics
Pages 439–455
Language en
Keywords mesenkymala stamceller, cellmigration, stamcellsnisch, kollagen, intervertebral disk
Subject categories Cell and Molecular Biology, Cell biology, Morphology, Histology


Disc-degeneration is believed a major cause for lumbar pain. Previously, potential stem cell niches in the intervertebral disc (IVD) region, located adjacent to epiphyseal plate was reported. The aim of the study was to examine migration of mesenchymal stem cells (MSCs), extracellular matrix (ECM) architecture in a potential cellular migration route (CMR; area located between the niche and IVD) and in the IVD in non-degenerated lapine- and in human degenerated IVD tissues. Human MSCs (n = 3), human degenerated IVD tissues (n = 10) and lapine IVDs (n = 10) were collected. The samples were examined by immunohistochemistry for stem cell markers; CD90, OCT3/4, pre-chondrocytic marker; GDF5, catabolic markers; MMP9, MMP13, inflammatory marker; IL1R, cellular migration markers; SNAI1, SNAI2, adhesion markers; β1-INTEGRIN and DDR2. In addition, gene-expression analyses (Real time PCR) were performed on additional samples. Further, time lapse studies were performed with hMSCs cultured on aligned COLL-I-fibers-coated glass-slides in DMEM-LG, 10% human serum containing fibroblast growth factor (bFGF). Results: Presence of stem cells (CD90+, OCT3/4 + ), pre-chondocytic cells (GDF5 + )and cells positive for migration markers (SNAI1+, SNAI2 + ), catabolic markers (MMP9+, MMP13 + ), inflammatory marker (IL1R + ), adhesion markers (DDR2+, B1-INTEGRIN + ) were detected (gene- and protein level) in investigated CMR and IVD regions. In the time lapse studies, MSCs alignment and protrusions were observed orientated in the same direction as collagen fibres. Results displays influence of ECM collagen architecture and collagen fiber spatial direction on migration of stem cells. The results can be useful when developing tissue-engineering strategies for disc-degeneration.

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